Nicarbazin has been used for over 50 years to control coccidiosis, an infection of protozoan parasites, in domestic poultry (see review by Chapman, 2001). While the exact mode of action of is unknown, several biochemical effects have been reported. One of the most acknowledged effects of nicarbazin on cells is to cause a leakage of potassium ions across the cell membrane along with an effect on mitochondrial energy production (Long, 1978). It is unclear how either of these effects influences the parasite itself, although nicarbazin has differential effects during the life cycle of the protozoan Eimeria—directly inhibiting both the asexual and sexual aspects of reproduction (Danforth, 1997; Xie, 1991).
In the poultry industry, nicarbazin is commonly administered to growing, meat-type chickens (e.g., broilers). However, when mistakenly added to the feed of egg-laying chickens, depigmentation of egg-shell color and egg production drop precipitously within a matter of days (Ott et al., 1956; Sherwood et al., 1956). These older studies clearly demonstrated a drug dosage effect among broiler-breeder hens; demonstrating that lower levels of nicarbazin (<125 ppm) produced a significant reduction in hatchability of fertile eggs. Higher levels (ca. 700 ppm) eliminated egg production entirely. However, all studies demonstrated that normal hatchability and egg production returned within 7-10 days following the removal of nicarbazin from the feed.
Chapman (2001) and others (e.g., Jones et al., 1990) suggest that nicarbazin functions to reduce hatchability of chicken eggs via the creation of ‘leaky membranes’ within the egg. Applicants have found that the main effect of nicarbazin was to alter the structure of the oocyte membrane by altering the structure and/or assembly of the primary protein composing the membrane (i.e., zona pellucida protein C (ZPC)). ZPC is also the primary sperm receptor among birds, mice, rats, cows and humans. Which thus would make the protocol useful in other animals besides just birds.
It is an object of the present invention to provide pharmaceutical compositions and methods for contraception in mammals.
It is yet another object of the invention to provide a method of contraception for animals and in particular, mammals, that is reversible.
It is yet another object of the invention to provide a method for animal contraception that may be orally administered, by for example, addition to feed of animals.
Other objects of the invention will become apparent from the description of the invention which follow.